Transcript Diapositiva 1

CONGENITAL SYPHILIS
Vanessa Salinas, MD
PL-1
• Syphilis is a chronic infection caused by the
spirochete T. pallidum, which is of particular
concern during pregnancy because of the risk of
transplacental infection of the fetus
• Congenital infection is associated with severe
adverse outcomes:
-perinatal death
-premature delivery
-Low birth weigth
-congenital anomalies
Modes of transmission
• Sexual contact
• Transplacental, from the mother to the
fetus
• By contact with a lesion at the time of
delivery
• The risk of developing syphilis after
contact is 40%
Risk factors for CS
• Lack or inadequate PNC
• Maternal substance abuse
• Failure to repeat a serologic test for
syphilis during the third trimester
• Treatment failure
• Inadequate access to STD’s clinics and
outreach activities
Epidemiology
The CS rate peaked in 1991 at 107.3 cases per 100,000 live births, and declined by 90.5%
to 10.2 cases/per 100,000 live births in 2002. The HP2010 objective for CS is 1.0 case per
100,000 live births. In 2002, 27 states, the District of Columbia, and one outlying area had rates
higher than this objective.
Adapted from CDC
CDC surveillance
• Before 1989 reported cases of CS were defined and
classified on the basis of clinical and serological features
known as the Kaufman criteria. The Kaufman criteria
were not designed for use as a surveillance case
definition.
• In 1988 CDC developed a surveillance case definition for
CS. This surveillance case definition differs from the
clinical diagnosis of CS in several ways. All infants born
to mothers who have untreated or inadequately treated
for syphilis are considered potentially infected.
Asymptomatic infants and stillbirths are included in the
case definition.
Maternal treatment history among 451 infants with
CS in US in 2002
PATHOGENESIS/PATHOLOGY
Syphilis in newborns
Congenital syphilis:
- Transplacental:
beginning 9 - 10 weeks
analogous to secondary adquired syphilis
affects bone, brain, liver, lung
placenta: large and thickened, hypercellular
UC abscess-like necrotic foci
- Vertical transmission:
more freq. primary and secondary dz.
Risk diminishes with after 4 years of infection
villi,
Syphilis in newborns
• 2/3 of NB with CS are asymptomatic at birth
• Overt infection can manifest in the fetus, the
newborn or late childhood
• The infant may have many or even no signs until
6-8 wks of life (delayed form)
• Clinical manifestations after birth are divided in:
-early CS <= 2 yo
-late CS >2 yo
Clinical manifestations of early CS
• The earliest sign of CS is nasal discharge (snuffles) that
occurs 1-2 weeks before the onset of the rash.
Treponemes abound in the discharge, providing a
definitive means of diagnosis.
• Secondary lesions on face; they first appeared during
the fourth postnatal week.
• The vesiculobullous eruption, known as pemphigus
syphiliticus, is highly distinctive when present. When the
bullae rupture, they leave a macerated, dusky red
surface that readily dries and crusts
• Other stigmata seen before the age of 2
years include maculopapular rash,
hepatosplenomegaly and jaundice.
Congenital syphilis. Diaphysitis with abundant callus formation secondary
to pathologic fractures through the metaphyseal lesions. The lesions healed,
and there were no sequelae
Clinical manifestations of late onset
• Hutchinson’s triad (63%):
– Hutchinson teeth (blunted upper incisors)
– Interstitial keratitis
– VII nerve deafness
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Frontal bossae (bony prominence of the forehead) 83%
Saddle nose 74%
Defect of hard pallate
Clutton’s joint (bilateral painless swelling of the knees)
Saber chins
Short maxillas
Protruding mandible
Laboratory diagnosis
• Direct visualization
• Serologic testing
Serologic Testing
1. The non-treponemal screening tests include
the VDRL (Venereal Disease Research
Laboratory), RPR (rapid plasma reagin), or
ART (automated reagin test).
- usually correlate with dz activity, in titers
- On the other hand, other disease states or
physiologic states, such as pregnancy, can
yield false-positive results.
Serologic Testing
2. Treponemal-specific tests including
fluorescent treponemal antibody absorption test
(FTA-ABS) or Treponema pallidum particle
agglutination (TP-PA) are necessary to confirm
the diagnosis of syphilis after a positive
nontreponemal test.
Nontreponemal screening during pregnancy is
recommended at the first prenatal visit, and
again in the third trimester, particularly in highrisk populations
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Adapted from Sexually Transmitted Diseases, by Holmes, Sparling, Mardh, et al.
Case definitions for CS
1. CONFIRMED OR DEFINITE CS
a. infant lesions
b. placenta
c. ummbilical cord
d. amniotic fluid
e. autopsy material
Case definitions for CS
2. PRESUMPTIVE OR PROBABLE,
if mother had:
a. untreated syphilis
b. no documentation of treatment
c. non penicillin therapy
d. penicillin <30 days before delivery
if baby has a reactive treponemal test and any of:
a. any evidence of CS on clinical exam
b. any evidence of CS on long bone radiograph
c. positive VDRL in CSF
d. abnormal CSF without any other cause
e. quantitative nontreponemal test titer >4 fold higher than maternal
titer
f. reactive treponemal antibody test beyond 15 months.
Case definitions for CS
3. POSSIBLE in asymptomatic infants when:
a. reactive treponemal or nontreponemal test
b. maternal tx during pregnancy s/ post-treatment fall
in titers
c. maternal tx before pregnancy s/ adequate follow up
“infants whose mothers were treated>1mo before
delivery AND had a documented fourfold decline in
titers AND have no evidence of reinfection or relapse,
are UNLIKELY to have the infection.”
Evaluation of neonates with
Suspected or Confirmed CS
1. Detailed physical examination
2. Quantitative nontrep. Test on infant
3. Specimens for testing for the presence of
spirochetes form mucocutaneous lesions
4. CBC to assess for anemia or
thrombocytopenia
5. CSF analysis
6. Long bone radiographs unless the diagnosis
has been confirmed otherwise
7. Pathologic examination of the placenta or UC.
Treatment
1. Definitive or probable CS
a) IV aqueous crystalline penicillin G x 1014 days 50 000UI/kg q 12hr (1-7 dol) and
q 8hr (8-30dol)
b) IM procaine penicillin G 50 000U/kg/dose
q day for 10 to 14 days
Treatment
2. Infants with probable syphilis, BUT who are
asymptomatic and c/ normal evaluation
a) If f/u is certain a single dose IM benzathine
penicillin G may be adequate
b) Some experts will prefer a 10-14 day full
course if any part of the evaluation is
abnormal or uninterpretable.
3. Asymp. Infants with possible CS.
a) single dose of benzathine penicillin
Follow up
1. Re-evaluation after treatment at 1, 2, 3, 6 and 12
months of age.
2. Nontreponemal tests should be repeated every 2 to 3
months until they have become nonreactive or
diminished four-fold.
3. Maternal origin Ab (nontreponemal) titers become
negative within 3 mo, and should become negative at 6
mo.
4. Treponemal-specific Ab of maternal origin persist for 12
to 15 mo IN 15% of uninfected infants from seropositive
mothers.
5. Congenital neurosyphilis should be evaluated (clinical
and CSF) every 6 months until CSF clears.
Follow up evaluation
• Non treponemal antibody serologic testing
should be checked at 1,3,6, 12 and 24
months following the treatmetn
• Titers should decrease by four fold by 6
months of therapy and became non
reactive by 12 or 24 months
• Titers that show a four fold rise or do not
decrease suggest either failure of
treatment or reinfection
• Sexually transmitted infections remain a major public health concern
in the
• United States. An estimated 19 million infections occur each year
• Sexually transmitted infections are relatively common during
pregnancy, especially
• in indigent, urban populations effected by drug abuse and
prostitution.
• Education, screening, treatment, and prevention are important
components of
• prenatal care for women at increased risk for these infections.
Treatment of these
• sexually transmitted infections is clearly associated with improved
pregnancy
• outcome and reductions in perinatal mortality
• Syphilis is caused by the spiroquete Treponema pallidum.
• Syphilis is primarily acquired through sexual contact,though
approximately 1000 cases of vertically acquired congenital
infections occur each year in the United States.
• Antepartum syphilis can profoundly affect pregnancy outcome by
causing
• preterm labor, fetal death, and neonatal infection by transplacental
or perinatal
• infection [8,9]. Fortunately, of the many congenital infections,
syphilis is not
• only the most readily prevented but also the most susceptible to
therapy.
DIAGNOSIS
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Diagnostic testing involves a two-step process, beginning with a nonspecific test and
concluding with a treponeme-specific test for patients screening positive.
The non-treponemal screening tests include the VDRL (Venereal Disease Research
Laboratory), RPR (rapid plasma reagin), or ART (automated reagin test).
Nontreponemal test antibody titers usually correlate with disease activity and should
be reported with a quantitative titer.
On the other hand, other disease states or physiologic states, such as pregnancy,
can yield false-positive results.
Because the current incidence of syphilis is so low, the majority of positive screening
tests are not due to treponemal infection.
Treponemal-specific tests including fluorescent treponemal antibody absorption test
(FTA-ABS) or Treponema pallidum particle agglutination (TP-PA) are necessary to
confirm the diagnosis of syphilis after a positive nontreponemal test. These tests are
specific for T pallidum antigens and are reported as positive or negative.
Nontreponemal screening during pregnancy is recommended at the first prenatal visit,
and again in the third trimester, particularly in high-risk populations
TREATMENT
• Penicillin G, in benzathine, aqueous procaine, or
aqueous crystalline form, is the drug of choice for
treatment of all stages of syphilis, and is the only
effective treatment for the prevention of congenital
syphilis in pregnancy.
• Erythromycin may be curative in the mother, but may not
prevent congenital syphilis because of the variability of
transplacental passage of the antibiotic.
• Ceftriaxone may prove useful in adults as an alternative
regimen for patients who have penicillin allergy;
however, there is insufficient information on its use in
pregnancy
• The efficacy of azithromycin in the penicillin-allergic
pregnant woman has not been adequately evaluated.
A recommended dosage regimen for pregnant women is as follows:
• Primary, secondary, or early latent stage: benzathine penicillin G,
2.4 million units intramuscularly (IM) in a single dose
• Late latent stage or syphilis of unknown duration: benzathine
penicillin G, 2.4 million units IM once a week for 3 consecutive
weeks
• Neurosyphilis: aqueous crystalline penicillin G, 3–4 million units
intravenously (IV) every 4 hours, or 18–24 million units daily as
continuous infusion, for 10–14 days
• The rate of treatment failure may be increased in pregnant patients
who have secondary syphilis, therefore some experts recommend
the use of a second injection of benzathine penicillin G 2.4 million
units IM 1 week after the first to treat early syphilis in pregnancy
• Within hours after treatment, patients can develop an acute
complication called the Jarisch-Herxheimer reaction. Symptoms
include fever, chills, myalgias, headache, tachycardia,
hyperventilation, vasodilation, and mild hypotension. Uterine
contractions and fetal heart rate decelerations may occur.
• Although the reaction occurs in 10% to 25% of patients overall, it is
most common in the treatment of early syphilis. A recent report [20]
noted an incidence of 40% among treated pregnant women.
Symptoms last for 12 to 24 hours and are usually self-limiting.
Patients can be treated symptomatically with antipyretics. Routine
hospitalization is not recommended for treatment during pregnancy,
though this has not been systematically evaluated [16].
Evaluation of treatment
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Consideration should be given to ultrasound evaluation of the fetus before
therapy when syphilis is diagnosed after 24 weeks. Ultrasound abnormalities
associated with syphilis include polyhydramnios, hepatosplenomegaly, ascites,
and hydrops [21]. Fetuses that have physical evidence of severe disease discovered
on ultrasound have also been shown to have biochemical evidence
of severe disease. Treatment failure and other complications are more common
among these fetuses [22]. When the fetal ultrasound is abnormal, consultation
with specialists in maternal-fetal medicine and neonatology should occur.
Complications
such as preterm labor, preterm premature rupture of the membranes,
fetal heart rate decelerations, and stillbirth may be precipitated by treatment.
In the severely affected fetus, particularly with preexisting fetal heart rate
abnormalities, consideration may be given to an untreated preterm or term
delivery followed by neonatal treatment [16,23]. Despite the advantages of
ultrasound assessment, maternal treatment should not be delayed unduly to obtain
imaging.